Elizabeth Mechcatie

In a large, national cohort study of U.S. veterans with non–dialysis dependent chronic kidney disease, lower systolic and diastolic blood pressures were associated with lower mortality rates – but only when the diastolic value was higher than about 70 mm Hg.

In addition, mortality rates were significantly increased among those patients with "ideal" blood pressure values (less than 130/80 mm Hg), "because of the inclusion of patients with low SBP and DBP," reported Dr. Csaba P. Kovesdy, chief of nephrology at the Memphis Veterans Affairs Medical Center, and his associates. The study was published in the Annals of Internal Medicine on Aug. 19  (Ann. Intern. Med. 2013;159:233-42).

The results indicate that current guidelines for patients with chronic kidney disease (CKD), which recommend a systolic blood pressure (SBP) of 130 mm Hg or lower "at the expense of lowering DBP [diastolic blood pressure] to less than approximately 70 mm Hg," may be harmful, they concluded. However, one of the limitations of the study was that it was an observational study and cannot establish a causal association, so "clinical trials are needed to inform us about the ideal BP target for antihypertensive therapy in patients with CKD," they added.

Using more than 18 million BP readings, the study evaluated the association of SBP and DBP values separately and SBP/DBP combinations on all-cause mortality in almost 652,000 U.S. veterans with CKD, who were not dependent on dialysis, between 2005 and 2012. Their mean age was 74 years, most were male (97%), 88% were white, 9% were black, 43% had coronary artery disease, and 43% had diabetes. The mean SBP values at baseline were 135 mm Hg while the mean DBP was 72 mm Hg; the mean glomerular filtration rate (GFR) was 50.4 mL/min per 1.73 m². The study looked at 96 different SBP/DBP combinations. During the time period of the study, 238,640 patients died.

They identified a U-shaped curve when analyzing mortality with SBP and DBP separately, "with both lower and higher levels showing a substantial and statistically significant association" with mortality risk. Based on the adjusted hazard ratios for the combinations of SBP and DBP, the lowest mortality rates were associated with blood pressures of 130-139/90-99 mm Hg, and 130-159/70-89 mm Hg, adjusted for factors that included age, sex, race, diabetes, and cardiovascular and cerebrovascular disease, age and medication use).

But combinations of lower SBP and DBP values "were associated with relatively lower mortality rates only if the lower DBP component was greater than approximately 70 mm Hg," they said.

When evaluating risk based on JNC 7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) categories,they found that that those with stage 1 hypertension (SBP of 140-159 mm Hg or DBP of 90-99 mm Hg) were associated with the lowest mortality rates, while those in the normal category (an SBP lower than 120 and a DBP below 80) had the highest mortality rates," results that were independent of confounding factors and were statistically significant.

The authors described an elevated SBP combined with a low DBP, which is common in CKD patients, as "an especially problematic BP pattern," they said, pointing out that 33% of the patients had an SBP greater than 140 mm Hg and a DBP less than 70 mm Hg at some point during the study period.

The study strengths included the large size and the representation of the U.S. veterans’ population, but the limitations included the mostly male population and the observational design of the study, so more studies are needed, the authors said. "Until such trials become available, low BP should be regarded as potentially deleterious in this patient population, and we suggest caution in lowering BP to less than what has been demonstrated as beneficial in randomized controlled trials," they concluded.

Dr. Kovesdy, professor of medicine at University of Tennessee Health Science Center, Memphis, disclosed having received grants from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, and nonfinancial support from the Department of Veterans Affairs while the study was conducted. Four authors had no disclosures, and one author disclosed having received NIH grants during the study. The remaining two authors disclosed having received research grants or personal fees from different pharmaceutical companies.

[email protected]

In a large, national cohort study of U.S. veterans with non–dialysis dependent chronic kidney disease, lower systolic and diastolic blood pressures were associated with lower mortality rates – but only when the diastolic value was higher than about 70 mm Hg.

In addition, mortality rates were significantly increased among those patients with "ideal" blood pressure values (less than 130/80 mm Hg), "because of the inclusion of patients with low SBP and DBP," reported Dr. Csaba P. Kovesdy, chief of nephrology at the Memphis Veterans Affairs Medical Center, and his associates. The study was published in the Annals of Internal Medicine on Aug. 19  (Ann. Intern. Med. 2013;159:233-42).

The results indicate that current guidelines for patients with chronic kidney disease (CKD), which recommend a systolic blood pressure (SBP) of 130 mm Hg or lower "at the expense of lowering DBP [diastolic blood pressure] to less than approximately 70 mm Hg," may be harmful, they concluded. However, one of the limitations of the study was that it was an observational study and cannot establish a causal association, so "clinical trials are needed to inform us about the ideal BP target for antihypertensive therapy in patients with CKD," they added.

Using more than 18 million BP readings, the study evaluated the association of SBP and DBP values separately and SBP/DBP combinations on all-cause mortality in almost 652,000 U.S. veterans with CKD, who were not dependent on dialysis, between 2005 and 2012. Their mean age was 74 years, most were male (97%), 88% were white, 9% were black, 43% had coronary artery disease, and 43% had diabetes. The mean SBP values at baseline were 135 mm Hg while the mean DBP was 72 mm Hg; the mean glomerular filtration rate (GFR) was 50.4 mL/min per 1.73 m². The study looked at 96 different SBP/DBP combinations. During the time period of the study, 238,640 patients died.

They identified a U-shaped curve when analyzing mortality with SBP and DBP separately, "with both lower and higher levels showing a substantial and statistically significant association" with mortality risk. Based on the adjusted hazard ratios for the combinations of SBP and DBP, the lowest mortality rates were associated with blood pressures of 130-139/90-99 mm Hg, and 130-159/70-89 mm Hg, adjusted for factors that included age, sex, race, diabetes, and cardiovascular and cerebrovascular disease, age and medication use).

But combinations of lower SBP and DBP values "were associated with relatively lower mortality rates only if the lower DBP component was greater than approximately 70 mm Hg," they said.

When evaluating risk based on JNC 7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) categories,they found that that those with stage 1 hypertension (SBP of 140-159 mm Hg or DBP of 90-99 mm Hg) were associated with the lowest mortality rates, while those in the normal category (an SBP lower than 120 and a DBP below 80) had the highest mortality rates," results that were independent of confounding factors and were statistically significant.

The authors described an elevated SBP combined with a low DBP, which is common in CKD patients, as "an especially problematic BP pattern," they said, pointing out that 33% of the patients had an SBP greater than 140 mm Hg and a DBP less than 70 mm Hg at some point during the study period.

The study strengths included the large size and the representation of the U.S. veterans’ population, but the limitations included the mostly male population and the observational design of the study, so more studies are needed, the authors said. "Until such trials become available, low BP should be regarded as potentially deleterious in this patient population, and we suggest caution in lowering BP to less than what has been demonstrated as beneficial in randomized controlled trials," they concluded.

Dr. Kovesdy, professor of medicine at University of Tennessee Health Science Center, Memphis, disclosed having received grants from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, and nonfinancial support from the Department of Veterans Affairs while the study was conducted. Four authors had no disclosures, and one author disclosed having received NIH grants during the study. The remaining two authors disclosed having received research grants or personal fees from different pharmaceutical companies.

[email protected]

In a large, national cohort study of U.S. veterans with non–dialysis dependent chronic kidney disease, lower systolic and diastolic blood pressures were associated with lower mortality rates – but only when the diastolic value was higher than about 70 mm Hg.

In addition, mortality rates were significantly increased among those patients with "ideal" blood pressure values (less than 130/80 mm Hg), "because of the inclusion of patients with low SBP and DBP," reported Dr. Csaba P. Kovesdy, chief of nephrology at the Memphis Veterans Affairs Medical Center, and his associates. The study was published in the Annals of Internal Medicine on Aug. 19  (Ann. Intern. Med. 2013;159:233-42).

The results indicate that current guidelines for patients with chronic kidney disease (CKD), which recommend a systolic blood pressure (SBP) of 130 mm Hg or lower "at the expense of lowering DBP [diastolic blood pressure] to less than approximately 70 mm Hg," may be harmful, they concluded. However, one of the limitations of the study was that it was an observational study and cannot establish a causal association, so "clinical trials are needed to inform us about the ideal BP target for antihypertensive therapy in patients with CKD," they added.

Using more than 18 million BP readings, the study evaluated the association of SBP and DBP values separately and SBP/DBP combinations on all-cause mortality in almost 652,000 U.S. veterans with CKD, who were not dependent on dialysis, between 2005 and 2012. Their mean age was 74 years, most were male (97%), 88% were white, 9% were black, 43% had coronary artery disease, and 43% had diabetes. The mean SBP values at baseline were 135 mm Hg while the mean DBP was 72 mm Hg; the mean glomerular filtration rate (GFR) was 50.4 mL/min per 1.73 m². The study looked at 96 different SBP/DBP combinations. During the time period of the study, 238,640 patients died.

They identified a U-shaped curve when analyzing mortality with SBP and DBP separately, "with both lower and higher levels showing a substantial and statistically significant association" with mortality risk. Based on the adjusted hazard ratios for the combinations of SBP and DBP, the lowest mortality rates were associated with blood pressures of 130-139/90-99 mm Hg, and 130-159/70-89 mm Hg, adjusted for factors that included age, sex, race, diabetes, and cardiovascular and cerebrovascular disease, age and medication use).

But combinations of lower SBP and DBP values "were associated with relatively lower mortality rates only if the lower DBP component was greater than approximately 70 mm Hg," they said.

When evaluating risk based on JNC 7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) categories,they found that that those with stage 1 hypertension (SBP of 140-159 mm Hg or DBP of 90-99 mm Hg) were associated with the lowest mortality rates, while those in the normal category (an SBP lower than 120 and a DBP below 80) had the highest mortality rates," results that were independent of confounding factors and were statistically significant.

The authors described an elevated SBP combined with a low DBP, which is common in CKD patients, as "an especially problematic BP pattern," they said, pointing out that 33% of the patients had an SBP greater than 140 mm Hg and a DBP less than 70 mm Hg at some point during the study period.

The study strengths included the large size and the representation of the U.S. veterans’ population, but the limitations included the mostly male population and the observational design of the study, so more studies are needed, the authors said. "Until such trials become available, low BP should be regarded as potentially deleterious in this patient population, and we suggest caution in lowering BP to less than what has been demonstrated as beneficial in randomized controlled trials," they concluded.

Dr. Kovesdy, professor of medicine at University of Tennessee Health Science Center, Memphis, disclosed having received grants from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, and nonfinancial support from the Department of Veterans Affairs while the study was conducted. Four authors had no disclosures, and one author disclosed having received NIH grants during the study. The remaining two authors disclosed having received research grants or personal fees from different pharmaceutical companies.

[email protected]

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

[email protected]

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

[email protected]

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

[email protected]

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel has unanimously recommended that riociguat, an orally administered potent vasodilator, should be approved for treating patients with pulmonary arterial hypertension (World Health Organization Group 1) and with chronic thromboembolic pulmonary hypertension (WHO Group 4), based on two phase-III international studies that found the drug was associated with significant improvements in the 6-minute walk test in these two groups of pulmonary hypertension patients.

At a meeting on August 6, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 11-0 that riociguat, the first in a new class of drugs, should be approved for these two groups of patients. The manufacturer, Bayer HealthCare Pharmaceuticals, has proposed that the drug be approved to improve exercise capacity, improve WHO functional class, delay clinical worsening in patients with PAH (WHO Group 1), and to improve exercise capacity and WHO functional class in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or with persistent or recurrent CTEPH after surgical treatment.

Riociguat is a soluble guanylate cyclase (sGC) stimulator and, if approved, it will be first treatment approved for CTEPH. The drug affects both pulmonary and systemic vascular resistance in pulmonary hypertension, which is associated with impaired synthesis of nitric oxide and insufficient stimulation of the nitric-oxide-sGC-cGMP pathway. Riociguat stimulates sGc, independent of nitric oxide, increasing the sensitivity of sGC to nitric oxide, according to Bayer.

The company presented the results of two double-blind, international studies, which randomized patients to riociguat or placebo, titrated from 0.5 mg to 2.5 mg three times a day, using the same endpoints and dosing titration strategy.

PATENT-1 (Pulmonary Arterial Hypertension sGC-stimulator Trial) compared riociguat with placebo in 380 mostly female patients (mean age, 51 years) with PAH. At 12 weeks, the change in the 6-minute walk test from baseline improved by a mean of 30 m among those treated with riociguat but dropped by a mean of 6 m in the placebo group. WHO functional class improved in 21% of those on riociguat, compared with 14% of those on placebo, and deteriorated in 4% of those on riociguat and 14% of those on placebo.

CHEST (Chronic Thomboembolic Pulmonary Hypertension sGC-Stimulator Trial) enrolled 261 patients with inoperable (WHO group 4) or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy; their mean age was 59 years, and about 61%-68% were female. At 16 weeks, the change in the 6-minute walk test from baseline improved by a mean of 39 m among those treated with riociguat but dropped by a mean of 6 m among those on placebo. WHO functional class improved in 33% of those on riociguat, compared with 15% of those on placebo, and deteriorated in 5% of those on riociguat and in 7% of those on placebo.

In both studies, there were statistically significant improvements in secondary clinically relevant endpoints.

In a pooled safety analysis of the two studies, the rates of adverse outcomes and serious adverse outcomes were similar in patients on the drug and those on placebo. The most common adverse events associated with treatment were headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea, and vomiting, according to Bayer.

Hypotension was higher among those on riociguat (10% vs 3.7%), with most cases mild to moderate. There were a few cases of hemoptysis in riociguat-treated patients (five cases in the two studies), which is included in the warning in the company’s proposed label.

The panel agreed that the effectiveness of the drug in the two studies was an adequate basis for approval of the two indications. Dr. Stuart Rich, professor of medicine at the University of Chicago, cautioned about the possible misuse of the drug in patients with CTEPH who could benefit from surgery and said that there should be measures in place to ensure that the drug is used to treat only those patients with CTEPH who are truly inoperable.

The panel members were not overly concerned about the effects of systemic vasodilation of the drug, although, once used in the general population outside of a controlled clinical trial, risks could increase in some patients, they pointed out.

Dr. Rich, an attending physician in the center for pulmonary hypertension at the University of Chicago Hospitals, said that there should be a strong warning pointing out that riociguat should never be used with inhaled nitric oxide, sublingual nitroglycerin, or a phosphodiesterase-5 (PDE- 5) inhibitor. His biggest concern is that it will be marketed as a new drug. "Physicians may not think that the mechanism [of riociguat] has similarities to the nitric oxide pathway, which in fact it really does," he said. Therefore, it is important that prescribers understand that, if those drugs were combined, they would be giving patients "a whopping dose of nitric oxide."

The FDA agreed with the company’s conclusions regarding the clinical trial results and supported the approval of the drug. The FDA review, however, raised the issue of hypotension associated with the higher dose and recommended capping the dose at 1.5 mg three times a day since the higher dose did not appear to add an incremental benefit, Dr. Preston Dunmon, a medical officer in the FDA’s division of cardiovascular and renal drug products, told the panel. But panelists said that there should be a broad range of doses to choose from and that the 2.5 mg t.i.d. dose should be available.

Currently, there is no drug approved for treating CTEPH. Bosentan (Tracleer), an endothelin receptor antagonist, and sildenafil (Revatio), a PDE-5 inhbitor, are approved for PAH (WHO Group 1). The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts before the meeting.

If approved, Bayer plans to market the drug as Adempas.

The results of the two studies were published in the July 25 issue of the New England Journal of Medicine (PATENT-1 [369:330-40]; CHEST-1 [369:319-29]).

[email protected]

SILVER SPRING, MD. – A Food and Drug Administration advisory panel has unanimously recommended that riociguat, an orally administered potent vasodilator, should be approved for treating patients with pulmonary arterial hypertension (World Health Organization Group 1) and with chronic thromboembolic pulmonary hypertension (WHO Group 4), based on two phase-III international studies that found the drug was associated with significant improvements in the 6-minute walk test in these two groups of pulmonary hypertension patients.

At a meeting on August 6, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 11-0 that riociguat, the first in a new class of drugs, should be approved for these two groups of patients. The manufacturer, Bayer HealthCare Pharmaceuticals, has proposed that the drug be approved to improve exercise capacity, improve WHO functional class, delay clinical worsening in patients with PAH (WHO Group 1), and to improve exercise capacity and WHO functional class in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or with persistent or recurrent CTEPH after surgical treatment.

Riociguat is a soluble guanylate cyclase (sGC) stimulator and, if approved, it will be first treatment approved for CTEPH. The drug affects both pulmonary and systemic vascular resistance in pulmonary hypertension, which is associated with impaired synthesis of nitric oxide and insufficient stimulation of the nitric-oxide-sGC-cGMP pathway. Riociguat stimulates sGc, independent of nitric oxide, increasing the sensitivity of sGC to nitric oxide, according to Bayer.

The company presented the results of two double-blind, international studies, which randomized patients to riociguat or placebo, titrated from 0.5 mg to 2.5 mg three times a day, using the same endpoints and dosing titration strategy.

PATENT-1 (Pulmonary Arterial Hypertension sGC-stimulator Trial) compared riociguat with placebo in 380 mostly female patients (mean age, 51 years) with PAH. At 12 weeks, the change in the 6-minute walk test from baseline improved by a mean of 30 m among those treated with riociguat but dropped by a mean of 6 m in the placebo group. WHO functional class improved in 21% of those on riociguat, compared with 14% of those on placebo, and deteriorated in 4% of those on riociguat and 14% of those on placebo.

CHEST (Chronic Thomboembolic Pulmonary Hypertension sGC-Stimulator Trial) enrolled 261 patients with inoperable (WHO group 4) or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy; their mean age was 59 years, and about 61%-68% were female. At 16 weeks, the change in the 6-minute walk test from baseline improved by a mean of 39 m among those treated with riociguat but dropped by a mean of 6 m among those on placebo. WHO functional class improved in 33% of those on riociguat, compared with 15% of those on placebo, and deteriorated in 5% of those on riociguat and in 7% of those on placebo.

In both studies, there were statistically significant improvements in secondary clinically relevant endpoints.

In a pooled safety analysis of the two studies, the rates of adverse outcomes and serious adverse outcomes were similar in patients on the drug and those on placebo. The most common adverse events associated with treatment were headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea, and vomiting, according to Bayer.

Hypotension was higher among those on riociguat (10% vs 3.7%), with most cases mild to moderate. There were a few cases of hemoptysis in riociguat-treated patients (five cases in the two studies), which is included in the warning in the company’s proposed label.

The panel agreed that the effectiveness of the drug in the two studies was an adequate basis for approval of the two indications. Dr. Stuart Rich, professor of medicine at the University of Chicago, cautioned about the possible misuse of the drug in patients with CTEPH who could benefit from surgery and said that there should be measures in place to ensure that the drug is used to treat only those patients with CTEPH who are truly inoperable.

The panel members were not overly concerned about the effects of systemic vasodilation of the drug, although, once used in the general population outside of a controlled clinical trial, risks could increase in some patients, they pointed out.

Dr. Rich, an attending physician in the center for pulmonary hypertension at the University of Chicago Hospitals, said that there should be a strong warning pointing out that riociguat should never be used with inhaled nitric oxide, sublingual nitroglycerin, or a phosphodiesterase-5 (PDE- 5) inhibitor. His biggest concern is that it will be marketed as a new drug. "Physicians may not think that the mechanism [of riociguat] has similarities to the nitric oxide pathway, which in fact it really does," he said. Therefore, it is important that prescribers understand that, if those drugs were combined, they would be giving patients "a whopping dose of nitric oxide."

The FDA agreed with the company’s conclusions regarding the clinical trial results and supported the approval of the drug. The FDA review, however, raised the issue of hypotension associated with the higher dose and recommended capping the dose at 1.5 mg three times a day since the higher dose did not appear to add an incremental benefit, Dr. Preston Dunmon, a medical officer in the FDA’s division of cardiovascular and renal drug products, told the panel. But panelists said that there should be a broad range of doses to choose from and that the 2.5 mg t.i.d. dose should be available.

Currently, there is no drug approved for treating CTEPH. Bosentan (Tracleer), an endothelin receptor antagonist, and sildenafil (Revatio), a PDE-5 inhbitor, are approved for PAH (WHO Group 1). The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts before the meeting.

If approved, Bayer plans to market the drug as Adempas.

The results of the two studies were published in the July 25 issue of the New England Journal of Medicine (PATENT-1 [369:330-40]; CHEST-1 [369:319-29]).

[email protected]

SILVER SPRING, MD. – A Food and Drug Administration advisory panel has unanimously recommended that riociguat, an orally administered potent vasodilator, should be approved for treating patients with pulmonary arterial hypertension (World Health Organization Group 1) and with chronic thromboembolic pulmonary hypertension (WHO Group 4), based on two phase-III international studies that found the drug was associated with significant improvements in the 6-minute walk test in these two groups of pulmonary hypertension patients.

At a meeting on August 6, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 11-0 that riociguat, the first in a new class of drugs, should be approved for these two groups of patients. The manufacturer, Bayer HealthCare Pharmaceuticals, has proposed that the drug be approved to improve exercise capacity, improve WHO functional class, delay clinical worsening in patients with PAH (WHO Group 1), and to improve exercise capacity and WHO functional class in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or with persistent or recurrent CTEPH after surgical treatment.

Riociguat is a soluble guanylate cyclase (sGC) stimulator and, if approved, it will be first treatment approved for CTEPH. The drug affects both pulmonary and systemic vascular resistance in pulmonary hypertension, which is associated with impaired synthesis of nitric oxide and insufficient stimulation of the nitric-oxide-sGC-cGMP pathway. Riociguat stimulates sGc, independent of nitric oxide, increasing the sensitivity of sGC to nitric oxide, according to Bayer.

The company presented the results of two double-blind, international studies, which randomized patients to riociguat or placebo, titrated from 0.5 mg to 2.5 mg three times a day, using the same endpoints and dosing titration strategy.

PATENT-1 (Pulmonary Arterial Hypertension sGC-stimulator Trial) compared riociguat with placebo in 380 mostly female patients (mean age, 51 years) with PAH. At 12 weeks, the change in the 6-minute walk test from baseline improved by a mean of 30 m among those treated with riociguat but dropped by a mean of 6 m in the placebo group. WHO functional class improved in 21% of those on riociguat, compared with 14% of those on placebo, and deteriorated in 4% of those on riociguat and 14% of those on placebo.

CHEST (Chronic Thomboembolic Pulmonary Hypertension sGC-Stimulator Trial) enrolled 261 patients with inoperable (WHO group 4) or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy; their mean age was 59 years, and about 61%-68% were female. At 16 weeks, the change in the 6-minute walk test from baseline improved by a mean of 39 m among those treated with riociguat but dropped by a mean of 6 m among those on placebo. WHO functional class improved in 33% of those on riociguat, compared with 15% of those on placebo, and deteriorated in 5% of those on riociguat and in 7% of those on placebo.

In both studies, there were statistically significant improvements in secondary clinically relevant endpoints.

In a pooled safety analysis of the two studies, the rates of adverse outcomes and serious adverse outcomes were similar in patients on the drug and those on placebo. The most common adverse events associated with treatment were headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea, and vomiting, according to Bayer.

Hypotension was higher among those on riociguat (10% vs 3.7%), with most cases mild to moderate. There were a few cases of hemoptysis in riociguat-treated patients (five cases in the two studies), which is included in the warning in the company’s proposed label.

The panel agreed that the effectiveness of the drug in the two studies was an adequate basis for approval of the two indications. Dr. Stuart Rich, professor of medicine at the University of Chicago, cautioned about the possible misuse of the drug in patients with CTEPH who could benefit from surgery and said that there should be measures in place to ensure that the drug is used to treat only those patients with CTEPH who are truly inoperable.

The panel members were not overly concerned about the effects of systemic vasodilation of the drug, although, once used in the general population outside of a controlled clinical trial, risks could increase in some patients, they pointed out.

Dr. Rich, an attending physician in the center for pulmonary hypertension at the University of Chicago Hospitals, said that there should be a strong warning pointing out that riociguat should never be used with inhaled nitric oxide, sublingual nitroglycerin, or a phosphodiesterase-5 (PDE- 5) inhibitor. His biggest concern is that it will be marketed as a new drug. "Physicians may not think that the mechanism [of riociguat] has similarities to the nitric oxide pathway, which in fact it really does," he said. Therefore, it is important that prescribers understand that, if those drugs were combined, they would be giving patients "a whopping dose of nitric oxide."

The FDA agreed with the company’s conclusions regarding the clinical trial results and supported the approval of the drug. The FDA review, however, raised the issue of hypotension associated with the higher dose and recommended capping the dose at 1.5 mg three times a day since the higher dose did not appear to add an incremental benefit, Dr. Preston Dunmon, a medical officer in the FDA’s division of cardiovascular and renal drug products, told the panel. But panelists said that there should be a broad range of doses to choose from and that the 2.5 mg t.i.d. dose should be available.

Currently, there is no drug approved for treating CTEPH. Bosentan (Tracleer), an endothelin receptor antagonist, and sildenafil (Revatio), a PDE-5 inhbitor, are approved for PAH (WHO Group 1). The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts before the meeting.

If approved, Bayer plans to market the drug as Adempas.

The results of the two studies were published in the July 25 issue of the New England Journal of Medicine (PATENT-1 [369:330-40]; CHEST-1 [369:319-29]).

[email protected]

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

[email protected]

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

[email protected]

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

[email protected]

The quadrivalent conjugate meningococcal vaccine Menveo is now licensed for use in children down to age 2 months, according to Novartis, the manufacturer.

Previously, Menveo (meningococcal group A, C, W-135 and Y conjugate vaccine) was licensed for children and adults aged 2-55 years. It was initially licensed in the United States in February 2010 for adolescents and adults aged 11-55 years, and the age was expanded down in January 2011. It is indicated for the prevention of meningococcal disease caused by four strains of the bacterium Neisseria meningitidis.

The approval was based on the results of three studies involving more than 8,700 infants in the United States, Australia, Canada, Latin America, and Taiwan, according to the statement from Novartis announcing the approval.

[email protected]

The quadrivalent conjugate meningococcal vaccine Menveo is now licensed for use in children down to age 2 months, according to Novartis, the manufacturer.

Previously, Menveo (meningococcal group A, C, W-135 and Y conjugate vaccine) was licensed for children and adults aged 2-55 years. It was initially licensed in the United States in February 2010 for adolescents and adults aged 11-55 years, and the age was expanded down in January 2011. It is indicated for the prevention of meningococcal disease caused by four strains of the bacterium Neisseria meningitidis.

The approval was based on the results of three studies involving more than 8,700 infants in the United States, Australia, Canada, Latin America, and Taiwan, according to the statement from Novartis announcing the approval.

[email protected]

The quadrivalent conjugate meningococcal vaccine Menveo is now licensed for use in children down to age 2 months, according to Novartis, the manufacturer.

Previously, Menveo (meningococcal group A, C, W-135 and Y conjugate vaccine) was licensed for children and adults aged 2-55 years. It was initially licensed in the United States in February 2010 for adolescents and adults aged 11-55 years, and the age was expanded down in January 2011. It is indicated for the prevention of meningococcal disease caused by four strains of the bacterium Neisseria meningitidis.

The approval was based on the results of three studies involving more than 8,700 infants in the United States, Australia, Canada, Latin America, and Taiwan, according to the statement from Novartis announcing the approval.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA’s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks –which are already in the labels of NSAIDs – will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA’s MedWatch program or by calling 800-332-1088.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA’s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks –which are already in the labels of NSAIDs – will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA’s MedWatch program or by calling 800-332-1088.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA’s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks –which are already in the labels of NSAIDs – will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA’s MedWatch program or by calling 800-332-1088.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

©Ingram Publishing/thinkstockphotos.com

Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA�s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks- which are already in the labels of NSAIDs- will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA's MedWatch program or by calling 800-332-1088.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

©Ingram Publishing/thinkstockphotos.com

Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA�s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks- which are already in the labels of NSAIDs- will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA's MedWatch program or by calling 800-332-1088.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

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Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA�s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks- which are already in the labels of NSAIDs- will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA's MedWatch program or by calling 800-332-1088.

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Short-term outcomes after carotid artery stenting followed by open heart surgery were comparable with those after carotid endarterectomy and open heart surgery performed at the same time, in a retrospective study that compared three approaches with treating patients who had both severe carotid artery disease and coronary artery disease.

However, after 1 year, staged carotid artery stenting and open heart surgery (CAS-OHS) "appears to be a better choice," with a significantly lower risk in the primary composite endpoint of death, stroke, or myocardial infarction, reported Dr. Mehdi H. Shishehbor and his coauthors (J. Am. Coll. Cardiol. 2013 [doi:10.1016/j.jacc.2013.03.094]).

The primary composite endpoint after undergoing CAS-OHS or combined carotid endarterectomy and OHS (CEA-OHS) were similar in both groups.

The third approach studied was carotid endarterectomy (CEA) followed by open heart surgery (staged CEA-OHS), which had the least favorable outcomes of all three approaches, with a "substantial risk of interstage MI," they reported. This approach, therefore, "should be avoided if possible," they concluded in the studywhich was published online on July 31, in the Journal of the American College of Cardiology Cardiovascular Interventions. Dr. Shishehbor is director of endovascular services in the Miller Family Heart and Vascular Institute at the Cleveland Clinic.

The study evaluated outcomes among 350 patients with severe carotid artery stenosis and were candidates for OHS, who underwent carotid revascularization within 90 days of having open heart surgery, at the Cleveland Clinic from 1997 to 2009: 45 had staged CEA-OHS, 195 had combined CEA-OHS, and 110 has staged CAS-OHS. Most of the open heart surgeries were coronary artery bypass grafting procedures.

Based on their analyses, they determined that in the short term, the composite endpoint was similar between those in the staged CAS-OHS group and those in the combined CEA-OHS group – although those in the CAS-OHS group had more MIs, most of which were between the procedures, and those in the combined CEA-OHS group has more perioperative strokes.

Of all three approaches, short-term outcomes were worse in the staged CEA-OHS group, because of the significantly higher risk of interstage MIs.

After 1 year, those in the staged CAS-OHS group had a significantly lower risk of the composite outcomes, compared with the other two groups: a 65% lower risk, compared with those in the combined CEA-OHS group; and a 67% lower risk, compared with those in the staged CAS-OHS group. The risk in the composite outcomes after 1 year in the two CEA groups was similar. Mortality after 1 year was similar in the three groups.

"In choosing between staged CAS-OHS and combined CEA-OHS, the increased risk of interstage MI with the former and perioperative stroke with the latter are important considerations despite similar risks for the early composite endpoint," the authors noted.

"Our study shows that carotid stenting followed by open heart surgery should be the first line strategy for treating patients with severe carotid and coronary disease, if the three- to four-week wait between procedures is clinically acceptable," Dr. Shishehbor said in a statement issued by the Cleveland Clinic. Although there has never been a randomized trial to determine what the best approach is for the types of patients in the study, "the evidence in this study may be enough to change practice," he added.

In fact, as a result of the study findings, changes are being made to the way patients with severe carotid and coronary artery disease are being managed at the Cleveland Clinic, and "we are collaborating across disciplines to identify the lowest risk treatment option for each patient," he added.

In the United States, currently, only 3% of patients with severe carotid and coronary artery disease are treated with staged carotid stenting followed by open heart surgery – compared with 31% of the patients in this study, the statement points out.

[email protected]

Short-term outcomes after carotid artery stenting followed by open heart surgery were comparable with those after carotid endarterectomy and open heart surgery performed at the same time, in a retrospective study that compared three approaches with treating patients who had both severe carotid artery disease and coronary artery disease.

However, after 1 year, staged carotid artery stenting and open heart surgery (CAS-OHS) "appears to be a better choice," with a significantly lower risk in the primary composite endpoint of death, stroke, or myocardial infarction, reported Dr. Mehdi H. Shishehbor and his coauthors (J. Am. Coll. Cardiol. 2013 [doi:10.1016/j.jacc.2013.03.094]).

The primary composite endpoint after undergoing CAS-OHS or combined carotid endarterectomy and OHS (CEA-OHS) were similar in both groups.

The third approach studied was carotid endarterectomy (CEA) followed by open heart surgery (staged CEA-OHS), which had the least favorable outcomes of all three approaches, with a "substantial risk of interstage MI," they reported. This approach, therefore, "should be avoided if possible," they concluded in the studywhich was published online on July 31, in the Journal of the American College of Cardiology Cardiovascular Interventions. Dr. Shishehbor is director of endovascular services in the Miller Family Heart and Vascular Institute at the Cleveland Clinic.

The study evaluated outcomes among 350 patients with severe carotid artery stenosis and were candidates for OHS, who underwent carotid revascularization within 90 days of having open heart surgery, at the Cleveland Clinic from 1997 to 2009: 45 had staged CEA-OHS, 195 had combined CEA-OHS, and 110 has staged CAS-OHS. Most of the open heart surgeries were coronary artery bypass grafting procedures.

Based on their analyses, they determined that in the short term, the composite endpoint was similar between those in the staged CAS-OHS group and those in the combined CEA-OHS group – although those in the CAS-OHS group had more MIs, most of which were between the procedures, and those in the combined CEA-OHS group has more perioperative strokes.

Of all three approaches, short-term outcomes were worse in the staged CEA-OHS group, because of the significantly higher risk of interstage MIs.

After 1 year, those in the staged CAS-OHS group had a significantly lower risk of the composite outcomes, compared with the other two groups: a 65% lower risk, compared with those in the combined CEA-OHS group; and a 67% lower risk, compared with those in the staged CAS-OHS group. The risk in the composite outcomes after 1 year in the two CEA groups was similar. Mortality after 1 year was similar in the three groups.

"In choosing between staged CAS-OHS and combined CEA-OHS, the increased risk of interstage MI with the former and perioperative stroke with the latter are important considerations despite similar risks for the early composite endpoint," the authors noted.

"Our study shows that carotid stenting followed by open heart surgery should be the first line strategy for treating patients with severe carotid and coronary disease, if the three- to four-week wait between procedures is clinically acceptable," Dr. Shishehbor said in a statement issued by the Cleveland Clinic. Although there has never been a randomized trial to determine what the best approach is for the types of patients in the study, "the evidence in this study may be enough to change practice," he added.

In fact, as a result of the study findings, changes are being made to the way patients with severe carotid and coronary artery disease are being managed at the Cleveland Clinic, and "we are collaborating across disciplines to identify the lowest risk treatment option for each patient," he added.

In the United States, currently, only 3% of patients with severe carotid and coronary artery disease are treated with staged carotid stenting followed by open heart surgery – compared with 31% of the patients in this study, the statement points out.

[email protected]

Short-term outcomes after carotid artery stenting followed by open heart surgery were comparable with those after carotid endarterectomy and open heart surgery performed at the same time, in a retrospective study that compared three approaches with treating patients who had both severe carotid artery disease and coronary artery disease.

However, after 1 year, staged carotid artery stenting and open heart surgery (CAS-OHS) "appears to be a better choice," with a significantly lower risk in the primary composite endpoint of death, stroke, or myocardial infarction, reported Dr. Mehdi H. Shishehbor and his coauthors (J. Am. Coll. Cardiol. 2013 [doi:10.1016/j.jacc.2013.03.094]).

The primary composite endpoint after undergoing CAS-OHS or combined carotid endarterectomy and OHS (CEA-OHS) were similar in both groups.

The third approach studied was carotid endarterectomy (CEA) followed by open heart surgery (staged CEA-OHS), which had the least favorable outcomes of all three approaches, with a "substantial risk of interstage MI," they reported. This approach, therefore, "should be avoided if possible," they concluded in the studywhich was published online on July 31, in the Journal of the American College of Cardiology Cardiovascular Interventions. Dr. Shishehbor is director of endovascular services in the Miller Family Heart and Vascular Institute at the Cleveland Clinic.

The study evaluated outcomes among 350 patients with severe carotid artery stenosis and were candidates for OHS, who underwent carotid revascularization within 90 days of having open heart surgery, at the Cleveland Clinic from 1997 to 2009: 45 had staged CEA-OHS, 195 had combined CEA-OHS, and 110 has staged CAS-OHS. Most of the open heart surgeries were coronary artery bypass grafting procedures.

Based on their analyses, they determined that in the short term, the composite endpoint was similar between those in the staged CAS-OHS group and those in the combined CEA-OHS group – although those in the CAS-OHS group had more MIs, most of which were between the procedures, and those in the combined CEA-OHS group has more perioperative strokes.

Of all three approaches, short-term outcomes were worse in the staged CEA-OHS group, because of the significantly higher risk of interstage MIs.

After 1 year, those in the staged CAS-OHS group had a significantly lower risk of the composite outcomes, compared with the other two groups: a 65% lower risk, compared with those in the combined CEA-OHS group; and a 67% lower risk, compared with those in the staged CAS-OHS group. The risk in the composite outcomes after 1 year in the two CEA groups was similar. Mortality after 1 year was similar in the three groups.

"In choosing between staged CAS-OHS and combined CEA-OHS, the increased risk of interstage MI with the former and perioperative stroke with the latter are important considerations despite similar risks for the early composite endpoint," the authors noted.

"Our study shows that carotid stenting followed by open heart surgery should be the first line strategy for treating patients with severe carotid and coronary disease, if the three- to four-week wait between procedures is clinically acceptable," Dr. Shishehbor said in a statement issued by the Cleveland Clinic. Although there has never been a randomized trial to determine what the best approach is for the types of patients in the study, "the evidence in this study may be enough to change practice," he added.

In fact, as a result of the study findings, changes are being made to the way patients with severe carotid and coronary artery disease are being managed at the Cleveland Clinic, and "we are collaborating across disciplines to identify the lowest risk treatment option for each patient," he added.

In the United States, currently, only 3% of patients with severe carotid and coronary artery disease are treated with staged carotid stenting followed by open heart surgery – compared with 31% of the patients in this study, the statement points out.

[email protected]

Between 1995 and 2009, the use of chest x-rays for children with asthma significantly increased in emergency departments overall, but dropped in pediatric emergency departments – findings that have implications for savings in health care costs and safety, according to Dr. Jane F. Knapp and her associates.

Citing factors that include the average cost of a chest x-ray ($370), the average time that obtaining an x-ray adds to an ED visit (27 minutes), and evidence that many children with respiratory illnesses can be treated safely and effectively without an x-ray, the authors pointed out that "reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure." The results of the retrospective study appear in the August issue of Pediatrics (2013;132:245-52).

Dr. Knapp of Children’s Mercy Hospitals and Clinics, Kansas City, Mo., and her coauthors used national survey data on ED visits from a sample of nonfederal, general, and short-stay hospitals in the United States to compare the rates of x-ray use for three groups of children evaluated between 1995 and 2009: those with moderate to severe asthma, aged 2-18 years; children with bronchiolitis, aged 3 months to 1 year; and children with croup, aged 3 months to 6 years.

During this period, the use of x-rays did not change significantly for the groups with bronchiolitis and croup. But the use of x-rays for children with asthma increased every year, about 7% a year (OR, 1.07). Although this annual increase appears small, it added up to a 2.4-fold increase over the period of time studied, the authors said.

"...Reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure."

In pediatric EDs specifically, the use of x-rays significantly decreased during the period studied for all three respiratory illnesses: asthma (OR, 0.44), bronchiolitis (OR, 0.37), and croup (OR, 0.34). A look at trends according to region showed that the use of x-rays in EDs for all three conditions increased significantly in the Midwest and South compared with the Northeast. In the West, use increased significantly for those with asthma and bronchiolitis only.

The increase in x-ray use among the children with asthma could not be explained by changes in the National Asthma Education and Prevention Program guidelines. The researchers speculated that some factors related to parents, patients, and physicians. They cited evidence that physicians are more likely to order antibiotics for a child or an x-ray for a respiratory illness or low back pain when parents or patients expect such measures. "Pressures on ED physicians to practice more aggressively could also be involved," they wrote.

Although the National Heart, Lung, and Blood Institute guidelines on the use of chest x-rays in children with asthma did not change during the study period, "we also believe that they do not provide the criteria that are sufficiently explicit to affect the discretionary use of x-rays," Dr Knapp and her associates said.

 “As we discussed in the article, we need to understand the reasons why more x-rays are being used over time in the ED care of the child with asthma rather than less. The reasons may be multifactorial, but just as we have worked to limit the overuse of antibiotics with guidelines, parental education, and individual and system performance evaluation, we need to find ways to limit the excess radiation and cost associated with the use of x-rays," Dr. Knapp said in an interview.

There are almost 1 million ED visits per year for pediatric asthma, bronchiolitis, and croup, they noted.

The study did not receive external funding and the authors had no disclosures.

[email protected]

This story was updated. 8/5/2013

Between 1995 and 2009, the use of chest x-rays for children with asthma significantly increased in emergency departments overall, but dropped in pediatric emergency departments – findings that have implications for savings in health care costs and safety, according to Dr. Jane F. Knapp and her associates.

Citing factors that include the average cost of a chest x-ray ($370), the average time that obtaining an x-ray adds to an ED visit (27 minutes), and evidence that many children with respiratory illnesses can be treated safely and effectively without an x-ray, the authors pointed out that "reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure." The results of the retrospective study appear in the August issue of Pediatrics (2013;132:245-52).

Dr. Knapp of Children’s Mercy Hospitals and Clinics, Kansas City, Mo., and her coauthors used national survey data on ED visits from a sample of nonfederal, general, and short-stay hospitals in the United States to compare the rates of x-ray use for three groups of children evaluated between 1995 and 2009: those with moderate to severe asthma, aged 2-18 years; children with bronchiolitis, aged 3 months to 1 year; and children with croup, aged 3 months to 6 years.

During this period, the use of x-rays did not change significantly for the groups with bronchiolitis and croup. But the use of x-rays for children with asthma increased every year, about 7% a year (OR, 1.07). Although this annual increase appears small, it added up to a 2.4-fold increase over the period of time studied, the authors said.

"...Reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure."

In pediatric EDs specifically, the use of x-rays significantly decreased during the period studied for all three respiratory illnesses: asthma (OR, 0.44), bronchiolitis (OR, 0.37), and croup (OR, 0.34). A look at trends according to region showed that the use of x-rays in EDs for all three conditions increased significantly in the Midwest and South compared with the Northeast. In the West, use increased significantly for those with asthma and bronchiolitis only.

The increase in x-ray use among the children with asthma could not be explained by changes in the National Asthma Education and Prevention Program guidelines. The researchers speculated that some factors related to parents, patients, and physicians. They cited evidence that physicians are more likely to order antibiotics for a child or an x-ray for a respiratory illness or low back pain when parents or patients expect such measures. "Pressures on ED physicians to practice more aggressively could also be involved," they wrote.

Although the National Heart, Lung, and Blood Institute guidelines on the use of chest x-rays in children with asthma did not change during the study period, "we also believe that they do not provide the criteria that are sufficiently explicit to affect the discretionary use of x-rays," Dr Knapp and her associates said.

 “As we discussed in the article, we need to understand the reasons why more x-rays are being used over time in the ED care of the child with asthma rather than less. The reasons may be multifactorial, but just as we have worked to limit the overuse of antibiotics with guidelines, parental education, and individual and system performance evaluation, we need to find ways to limit the excess radiation and cost associated with the use of x-rays," Dr. Knapp said in an interview.

There are almost 1 million ED visits per year for pediatric asthma, bronchiolitis, and croup, they noted.

The study did not receive external funding and the authors had no disclosures.

[email protected]

This story was updated. 8/5/2013

Between 1995 and 2009, the use of chest x-rays for children with asthma significantly increased in emergency departments overall, but dropped in pediatric emergency departments – findings that have implications for savings in health care costs and safety, according to Dr. Jane F. Knapp and her associates.

Citing factors that include the average cost of a chest x-ray ($370), the average time that obtaining an x-ray adds to an ED visit (27 minutes), and evidence that many children with respiratory illnesses can be treated safely and effectively without an x-ray, the authors pointed out that "reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure." The results of the retrospective study appear in the August issue of Pediatrics (2013;132:245-52).

Dr. Knapp of Children’s Mercy Hospitals and Clinics, Kansas City, Mo., and her coauthors used national survey data on ED visits from a sample of nonfederal, general, and short-stay hospitals in the United States to compare the rates of x-ray use for three groups of children evaluated between 1995 and 2009: those with moderate to severe asthma, aged 2-18 years; children with bronchiolitis, aged 3 months to 1 year; and children with croup, aged 3 months to 6 years.

During this period, the use of x-rays did not change significantly for the groups with bronchiolitis and croup. But the use of x-rays for children with asthma increased every year, about 7% a year (OR, 1.07). Although this annual increase appears small, it added up to a 2.4-fold increase over the period of time studied, the authors said.

"...Reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure."

In pediatric EDs specifically, the use of x-rays significantly decreased during the period studied for all three respiratory illnesses: asthma (OR, 0.44), bronchiolitis (OR, 0.37), and croup (OR, 0.34). A look at trends according to region showed that the use of x-rays in EDs for all three conditions increased significantly in the Midwest and South compared with the Northeast. In the West, use increased significantly for those with asthma and bronchiolitis only.

The increase in x-ray use among the children with asthma could not be explained by changes in the National Asthma Education and Prevention Program guidelines. The researchers speculated that some factors related to parents, patients, and physicians. They cited evidence that physicians are more likely to order antibiotics for a child or an x-ray for a respiratory illness or low back pain when parents or patients expect such measures. "Pressures on ED physicians to practice more aggressively could also be involved," they wrote.

Although the National Heart, Lung, and Blood Institute guidelines on the use of chest x-rays in children with asthma did not change during the study period, "we also believe that they do not provide the criteria that are sufficiently explicit to affect the discretionary use of x-rays," Dr Knapp and her associates said.

 “As we discussed in the article, we need to understand the reasons why more x-rays are being used over time in the ED care of the child with asthma rather than less. The reasons may be multifactorial, but just as we have worked to limit the overuse of antibiotics with guidelines, parental education, and individual and system performance evaluation, we need to find ways to limit the excess radiation and cost associated with the use of x-rays," Dr. Knapp said in an interview.

There are almost 1 million ED visits per year for pediatric asthma, bronchiolitis, and croup, they noted.

The study did not receive external funding and the authors had no disclosures.

[email protected]

This story was updated. 8/5/2013

Between 1995 and 2009, the use of chest x-rays for children with asthma significantly increased in emergency departments overall, but dropped in pediatric emergency departments – findings that have implications for savings in health care costs and safety, according to Dr. Jane F. Knapp and her associates.

Citing factors that include the average cost of a chest x-ray ($370), the average time that obtaining an x-ray adds to an ED visit (27 minutes), and evidence that many children with respiratory illnesses can be treated safely and effectively without an x-ray, the authors pointed out that "reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure." The results of the retrospective study appear in the August issue of Pediatrics (2013;132:245-52).

Dr. Knapp of Children’s Mercy Hospitals and Clinics, Kansas City, Mo., and her coauthors used national survey data on ED visits from a sample of nonfederal, general, and short-stay hospitals in the United States to compare the rates of x-ray use for three groups of children evaluated between 1995 and 2009: those with moderate to severe asthma, aged 2-18 years; children with bronchiolitis, aged 3 months to 1 year; and children with croup, aged 3 months to 6 years.

During this period, the use of x-rays did not change significantly for the groups with bronchiolitis and croup. But the use of x-rays for children with asthma increased every year, about 7% a year (OR, 1.07). Although this annual increase appears small, it added up to a 2.4-fold increase over the period of time studied, the authors said.

"...Reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure."

In pediatric EDs specifically, the use of x-rays significantly decreased during the period studied for all three respiratory illnesses: asthma (OR, 0.44), bronchiolitis (OR, 0.37), and croup (OR, 0.34). A look at trends according to region showed that the use of x-rays in EDs for all three conditions increased significantly in the Midwest and South compared with the Northeast. In the West, use increased significantly for those with asthma and bronchiolitis only.

The increase in x-ray use among the children with asthma could not be explained by changes in the National Asthma Education and Prevention Program guidelines. The researchers speculated that some factors related to parents, patients, and physicians. They cited evidence that physicians are more likely to order antibiotics for a child or an x-ray for a respiratory illness or low back pain when parents or patients expect such measures. "Pressures on ED physicians to practice more aggressively could also be involved," they wrote.

Although the National Heart, Lung, and Blood Institute guidelines on the use of chest x-rays in children with asthma did not change during the study period, "we also believe that they do not provide the criteria that are sufficiently explicit to affect the discretionary use of x-rays," Dr Knapp and her associates said.

 “As we discussed in the article, we need to understand the reasons why more x-rays are being used over time in the ED care of the child with asthma rather than less. The reasons may be multifactorial, but just as we have worked to limit the overuse of antibiotics with guidelines, parental education, and individual and system performance evaluation, we need to find ways to limit the excess radiation and cost associated with the use of x-rays," Dr. Knapp said in an interview.

There are almost 1 million ED visits per year for pediatric asthma, bronchiolitis, and croup, they noted.

The study did not receive external funding and the authors had no disclosures.

[email protected]

This story was updated. 8/5/2013

Between 1995 and 2009, the use of chest x-rays for children with asthma significantly increased in emergency departments overall, but dropped in pediatric emergency departments – findings that have implications for savings in health care costs and safety, according to Dr. Jane F. Knapp and her associates.

Citing factors that include the average cost of a chest x-ray ($370), the average time that obtaining an x-ray adds to an ED visit (27 minutes), and evidence that many children with respiratory illnesses can be treated safely and effectively without an x-ray, the authors pointed out that "reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure." The results of the retrospective study appear in the August issue of Pediatrics (2013;132:245-52).

Dr. Knapp of Children’s Mercy Hospitals and Clinics, Kansas City, Mo., and her coauthors used national survey data on ED visits from a sample of nonfederal, general, and short-stay hospitals in the United States to compare the rates of x-ray use for three groups of children evaluated between 1995 and 2009: those with moderate to severe asthma, aged 2-18 years; children with bronchiolitis, aged 3 months to 1 year; and children with croup, aged 3 months to 6 years.

During this period, the use of x-rays did not change significantly for the groups with bronchiolitis and croup. But the use of x-rays for children with asthma increased every year, about 7% a year (OR, 1.07). Although this annual increase appears small, it added up to a 2.4-fold increase over the period of time studied, the authors said.

"...Reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure."

In pediatric EDs specifically, the use of x-rays significantly decreased during the period studied for all three respiratory illnesses: asthma (OR, 0.44), bronchiolitis (OR, 0.37), and croup (OR, 0.34). A look at trends according to region showed that the use of x-rays in EDs for all three conditions increased significantly in the Midwest and South compared with the Northeast. In the West, use increased significantly for those with asthma and bronchiolitis only.

The increase in x-ray use among the children with asthma could not be explained by changes in the National Asthma Education and Prevention Program guidelines. The researchers speculated that some factors related to parents, patients, and physicians. They cited evidence that physicians are more likely to order antibiotics for a child or an x-ray for a respiratory illness or low back pain when parents or patients expect such measures. "Pressures on ED physicians to practice more aggressively could also be involved," they wrote.

Although the National Heart, Lung, and Blood Institute guidelines on the use of chest x-rays in children with asthma did not change during the study period, "we also believe that they do not provide the criteria that are sufficiently explicit to affect the discretionary use of x-rays," Dr Knapp and her associates said.

 “As we discussed in the article, we need to understand the reasons why more x-rays are being used over time in the ED care of the child with asthma rather than less. The reasons may be multifactorial, but just as we have worked to limit the overuse of antibiotics with guidelines, parental education, and individual and system performance evaluation, we need to find ways to limit the excess radiation and cost associated with the use of x-rays," Dr. Knapp said in an interview.

There are almost 1 million ED visits per year for pediatric asthma, bronchiolitis, and croup, they noted.

The study did not receive external funding and the authors had no disclosures.

[email protected]

This story was updated. 8/5/2013

Between 1995 and 2009, the use of chest x-rays for children with asthma significantly increased in emergency departments overall, but dropped in pediatric emergency departments – findings that have implications for savings in health care costs and safety, according to Dr. Jane F. Knapp and her associates.

Citing factors that include the average cost of a chest x-ray ($370), the average time that obtaining an x-ray adds to an ED visit (27 minutes), and evidence that many children with respiratory illnesses can be treated safely and effectively without an x-ray, the authors pointed out that "reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure." The results of the retrospective study appear in the August issue of Pediatrics (2013;132:245-52).

Dr. Knapp of Children’s Mercy Hospitals and Clinics, Kansas City, Mo., and her coauthors used national survey data on ED visits from a sample of nonfederal, general, and short-stay hospitals in the United States to compare the rates of x-ray use for three groups of children evaluated between 1995 and 2009: those with moderate to severe asthma, aged 2-18 years; children with bronchiolitis, aged 3 months to 1 year; and children with croup, aged 3 months to 6 years.

During this period, the use of x-rays did not change significantly for the groups with bronchiolitis and croup. But the use of x-rays for children with asthma increased every year, about 7% a year (OR, 1.07). Although this annual increase appears small, it added up to a 2.4-fold increase over the period of time studied, the authors said.

"...Reversing this trend could improve ED efficiency, decrease costs, and decrease radiation exposure."

In pediatric EDs specifically, the use of x-rays significantly decreased during the period studied for all three respiratory illnesses: asthma (OR, 0.44), bronchiolitis (OR, 0.37), and croup (OR, 0.34). A look at trends according to region showed that the use of x-rays in EDs for all three conditions increased significantly in the Midwest and South compared with the Northeast. In the West, use increased significantly for those with asthma and bronchiolitis only.

The increase in x-ray use among the children with asthma could not be explained by changes in the National Asthma Education and Prevention Program guidelines. The researchers speculated that some factors related to parents, patients, and physicians. They cited evidence that physicians are more likely to order antibiotics for a child or an x-ray for a respiratory illness or low back pain when parents or patients expect such measures. "Pressures on ED physicians to practice more aggressively could also be involved," they wrote.

Although the National Heart, Lung, and Blood Institute guidelines on the use of chest x-rays in children with asthma did not change during the study period, "we also believe that they do not provide the criteria that are sufficiently explicit to affect the discretionary use of x-rays," Dr Knapp and her associates said.

 “As we discussed in the article, we need to understand the reasons why more x-rays are being used over time in the ED care of the child with asthma rather than less. The reasons may be multifactorial, but just as we have worked to limit the overuse of antibiotics with guidelines, parental education, and individual and system performance evaluation, we need to find ways to limit the excess radiation and cost associated with the use of x-rays," Dr. Knapp said in an interview.

There are almost 1 million ED visits per year for pediatric asthma, bronchiolitis, and croup, they noted.

The study did not receive external funding and the authors had no disclosures.

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This story was updated. 8/5/2013